The Atroposelective Iodination of 2-Amino-6-arylpyridines Catalyzed by Chiral Disulfonimides Actually Proceeds via Brønsted Base Catalysis: A Combined Experimental, Computational, and Machine-Learning Study
Abstract
-iodosuccinimide is described. While initially hypothesized to proceed via Brønsted-acid catalysis through activation of NIS, experimental evidence led us to reconsider the possible function of the DSI catalyst. We now propose an unprecedented mechanism in which the conjugate base of the DSI functions instead as a Brønsted-base, with the rate- and stereodetermining step involving an enantioselective deprotonation of a Wheland intermediate. The experimental data was used to initiate a DFT exploration of the reaction mechanism, which, after thorough analysis of the transition state structures and reaction coordinate, confirmed our revised hypothesis. The unique structural features of the highest-performing catalyst were explored further with a chemoinformatics-based workflow, leading to a detailed elucidation of those factors contributing to the origin of enantioselection.
Fields of Study & Subjects
Axial and Atropisomeric Chirality Synthesis
Catalytic C–H Functionalization Methods
Catalytic Cross-Coupling Reactions
Publication details
- Journal / source
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Volume
- 148
- Issue
- 2
- Pages
- 2175–2190
- Publication date
- 6 January 2026
- Language
- EN